Allogeneic hematopoietic stem cell transplant is an established treatment modality for hematologic and non-hematologic diseases. However, it is associated with acute and long-term sequelae which can translate into mortality. Graft-versus-host disease (GVHD) remains a glaring obstacle, especially with the advent of reduced-intensity conditioning. Serotherapy capitalizes on antibodies which target T cells and other immune cells to mitigate this effect. This article focuses on the utility of two such agents: anti-thymocyte globulin (ATG) and alemtuzumab. ATG has demonstrated benefit in prophylaxis against GVHD, especially in the chronic presentation. However, there is limited impact of ATG on overall survival and it has little utility in the treatment context. There may be an initial improvement, particularly in skin manifestations, but no substantial benefit has been elicited. Alemtuzumab has shown benefit in both prophylaxis and treatment of GVHD, but at the consequence of a more profound immunosuppressive phase, mandating aggressive viral prophylaxis. There remains heterogeneity in the doses and regimens of the agents, with no standardized protocol in place. Furthermore, it seems that once steroid-refractory GVHD has been established, there is little that can be offered to offset the ultimately dismal outcome. Here we present a systematic overview of ATG- or alemtuzumab-based serotherapy in the prophylaxis and management of GVHD.

We describe a rare case of severe autoimmune haemolytic anaemia (AIHA) in the setting of underlying chronic lymphocytic leukaemia receiving intravenous immunoglobulin, history of warm IgG autoantibody and treatment with nivolumab for advanced non-small cell lung cancer. In this report, we describe AIHA as a potential serious immune-related adverse event from immune checkpoint inhibitors, discuss other potential contributing factors and review previously described cases of AIHA in patients receiving programmed death 1 (PD-1) inhibitors. In the era of immunotherapy, we hope to add literature to raise awareness of potential immune-related sequelae such as AIHA. We aim to highlight the importance of close monitoring for prompt identification and management of potentially fatal AIHA and immune-related adverse events of PD-1 inhibitors by holding immunotherapy and treating with high-dose steroids, particularly in subgroups which may be at increased risk.

Exploring the relationship between various neurotransmitters and breast cancer cell growth has revealed their likely centrality to improving breast cancer treatment. Neurotransmitters play a key role in breast cancer biology through their effects on the cell cycle, epithelial mesenchymal transition, angiogenesis, inflammation, the tumor microenvironment and other pathways. Neurotransmitters and their receptors are vital to the initiation, progression and drug resistance of cancer and progress in our biological understanding may point the way to lower-cost and lower-risk antitumor therapeutic strategies. This review discusses multiple neurotransmitters in the context of breast cancer. It also discusses risk factors, repurposing of pharmaceuticals impacting neurotransmitter pathways, and the opportunity for better integrated models that encompass exercise, the intestinal microbiome, and other non-pharmacologic considerations. Neurotransmitters’ role in breast cancer should no longer be ignored; it may appear to complicate the molecular picture but the ubiquity of neurotransmitters and their wide-ranging impacts provide an organizing framework upon which further understanding and progress against breast cancer can be based.

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574 Background: Pancreatic (PC) and biliary cancers (BC) are cold tumors with limited activity of single agent immune checkpoint inhibitors. DNA methyltransferase inhibitors (DNMTi) have immunomodulatory effects manifested by upregulation of interferon pathways and expression of endogenous retroviral signatures. We performed a phase Ib study of the DNMTi guadecitabine (G) and durvalumab (D) in patients (pts) with hepatocellular carcinoma, PC and BC. We report initial results from the PC and BC cohorts. Methods: This is a phase Ib study to establish the maximum tolerated dose (MTD) of the combination (dose escalation; 3+3 design) and evaluate the objective response rate (ORR) in expansion cohorts of PC and BC. G was given at escalating doses of 30 mg/m2 and 45 mg/m2 subQ for 5 days q 28 days. D was given at 1500 mg IV on day 8 of each cycle. Expansion was started at the MTD. Eligibility criteria included ECOG 0-1, ANC ≥ 1,500, platelets > 100,000, albumin ≥ 2.5 g/dL, total bilirubin ≤ 2.5 x upper limit of normal, failure of ≥ 1 prior line of therapy for advanced disease. Prior anti PD-1/PDL-1 was not allowed. Tumor biopsies were performed during screening and on cycle 3 day 1. Results: A total of 11 pts were treated in dose escalation; 3 at dose level 1, and 8 (6 evaluable for DLT) at dose level 2. Given lack of dose-limiting toxicities, MTD was the highest planned dose of G at 45 mg/m2. 24 pts with PC and 23 pts with BC were treated in dose escalation and expansion. For the PC cohort: median age was 66 (43, 93), 29% female, 67% ECOG 1, and median number of prior therapies 2 (1,3). For the BC cohort: median age was 61 (41, 85), 52% female, 78% ECOG 1, and median number of prior therapies 1 (1,3). All grade treatment related AEs in ≥10% of pts were neutropenia (55%), leukopenia (50%), anemia (33%), fatigue (33%), thrombocytopenia (17%), nausea (15%), and anorexia (10%). Grade 3/4 AEs in ≥10% of pts were neutropenia (40%), leukopenia (35%), and anemia (13%). There was 1(5%) PR in PC cohort lasting > 24 mo and ongoing and 1(5%) in BC cohort lasting 12 mo; both were in MSS pts. SD was noted in 7/24 (29%) PC and 5/23 (22%) BC pts, 8 of which lasted ≥4 mo. Median PFS for PC and BC was 2.1 mo [1.9, 3.8] and 1.9 mo [1.4, 2] respectively. Median OS for PC and BC was 4.4 mo [3.4, NR] and 8.6 mo [6.4, NR]. Six and 12 mo OS rates are 38% [21, 66] and 27% [13, 56] for PC; 69% [52, 91] and 35% [19, 63] for BC. 4% of PC pts and 42% of BC pts received another therapy after progression. Conclusions: The combination of G and D has a manageable safety profile in pts with advanced PC and BC; grade 3/4 AEs were limited to myelosuppression. The combination had limited clinical activity based on ORR and PFS in this unselected, pretreated population; however, a subset of pts appeared to derive prolonged clinical benefit, and OS rates were comparable to standard second line chemotherapy, despite a minority of pts receiving subsequent treatment. Biomarker analyses are ongoing. Clinical trial information: NCT03257761.